Management of acute seizure and status epilepticus Apisit Boongird, MD Division of Neurology Ramathibodi Hospital Sunday August 27, 2560 Topics • Acute repetitive seizure • Status epilepticus Definition of epileptic seizure by the International League Against Epilepsy (ILAE) • An epileptic seizure is a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Epilepsia, 46(4):470–472, 2005 Acute repetitive seizures (Seizure clusters) Acute repetitive seizures (ARS) • Home • OPD • IPD Acute Repetitive Seizures (ARS) • The practical definition of acute repetitive seizures has not been established. • Acute repetitive seizures is neurologic emergency and a common clinical phenomenon describing an increase in seizures occurring over a specific period of time (ranging from several minutes up to 24 hours). • Acute repetitive seizures may include any type of seizure and may vary in severity, but by definition there is complete recovery in between seizures. Curr Opin Neurol 2015;28(2):143Y150. Management of acute repetitive seizures (ARS) • Stop the seizures • Identify the etiology of acute repetitive seizures • Benzodiazepines remain the mainstay of therapy. • The treatment of ARS includes the usage of extra doses of usual antiepileptic medications and oral benzodiazepines (diazepam or lorazepam) for mild ARS. • A 45 yo presented with first unprovoked seizures a year ago. seizure type 1: left face clonic with preserved awareness seizure duration: 5 minutes treatment: LEV 500-500 + tumor removal • In August 2560, he had ARS for 2 hours. Outpatient acute benzodiazepine therapy • Rectal diazepam is the only currently marketed treatment available for use by nonmedical caregivers in the USA, and buccal midazolam is approved in the European Union. Outpatient acute benzodiazepine therapy Medications Formulation Notes Diazepam oral tablet rectal gel (FDA approved) N Engl J Med 1998; 338:1869–1875. and Neurology 1998; 51:1274–1282. intramuscular Midazolam buccal intranasal intramuscular N Engl J Med 2012; 366:591–600 (The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART) in pre-hospital status epilepticus Lorazepam oral tablet intranasal sublingual Progesterone cyclic natural progesterone catamenial epilepsy Neurology 2014; 83:345–348. CNS Drugs (2015) 29:55–70 Standard doses are indicated below: Carers should only administer a single dose of midazolam. If the seizure has not stopped within 10 minutes after Oromucosal midazolam (solution Buccolam) Age range Dose Label colour 3 to 6 months hospital setting 2.5 mg Yellow > 6 months to < 1 year 2.5 mg Yellow 1 year to < 5 years 5 mg Blue 5 years to < 10 years 7.5 mg Purple 10 years to < 18 years 10 mg Orange https://www.medicines.org.uk Status epilepticus (SE) Key points • Status epilepticus is a neurologic emergency with high morbidity and mortality. Its management requires immediate action and diligence to avoid pharmacoresistance and brain injury. • Status epilepticus represents the persistence of abnormal excitation and the ineffective recruitment of inhibition. J Clin Neurophysiol1995;12(4):326Y342. Old definition of SE • A definition of more than 30 minutes of continuous seizure activity or two or more sequential seizures without full recovery of consciousness between was widely adopted, citing neuronal damage in animal models beyond this timeframe. Epilepsy Foundation, 1993 Lothman 1990 Phase 1: compensation Cerebral changes Systemic and metabolic changes Autonomic and cardiovascular changes increased cerebral blood flow hyperglycemia increased blood pressure increased cerebral metabolism lactic acidosis increased cardiac output increased lactate concentration massive catecholamine release increased glucose concentration cardiac dysthymia urine incontinence J Neurol Neurosurg Psychiatry 2001;70(suppl II):ii22–ii27 Phase 2: decompensation Cerebral changes Systemic and metabolic changes Autonomic and cardiovascular changes failure of cerebral autoregulation hypoglycemia hypoxia hypoxia hypokalemia/ hyperkalemia falling blood pressure hypoglycemia metabolic and respiratory acidosis falling cardiac output increased intracranial pressure and hepatic and renal dysfunction cardiac failure cerebral oedema consumptive coagulopathy respiratory failure DIC hyperpyrexia rhabdomyolysis, myoglobinuria J Neurol Neurosurg Psychiatry 2001;70(suppl II):ii22–ii27 “Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1). It is a condition, which can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures”. Epilepsia, 56(10):1515–1523, 2015 Type of SE Operational dimension 1 Operational dimension 2 Time (t1), when a seizure is Time (t2), when a seizure may likely to cause long term consequences be prolonged leading to (including neuronal injury, continuous neuronal death, alteration seizure activity of neuronal networks and functional deficits) Tonic- clonic SE 5 min 30 min Focal SE with 10 min > 60 min impaired consciousness Absence status 10-15 mina unknown epilepticus a= Evidence for the time frame is currently limited and future data may lead to modifications Epilepsia, 56(10):1515–1523, 2015 Classification of SE by the ILAE • 1 Semiology • 2 Etiology • 3 EEG correlates • 4 Age Epilepsia, 56(10):1515–1523, 2015 Axis 1: Semiology • The presence or absence of prominent motor symptoms • The degree (qualitative or quantitative) of impaired consciousness Epilepsia, 56(10):1515–1523, 2015 Axis 1: Classification of status epilepticus (SE) A) With prominent motor symptoms A.1 Convulsive SE (CSE, synonym: tonic–clonic SE) A.1.a. Generalized convulsive A.1.b. Focal onset evolving into bilateral convulsive SE A.1.c. Unknown whether focal or generalized A.2 Myoclonic SE (prominent epileptic myoclonic jerks) A.2.a. With coma A.2.b. Without coma A.3 Focal motor A.3.a. Repeated focal motor seizures (Jacksonian) A.3.b. Epilepsia partialis continua (EPC) A.3.c. Adversive status A.3.d. Oculoclonic status A.3.e. Ictal paresis (i.e., focal inhibitory SE) A.4 Tonic status A.5 Hyperkinetic SE Epilepsia, 56(10):1515–1523, 2015 Axis 1: Classification of status epilepticus (SE) (B) Without prominent motor symptoms (i.e., non- convulsive SE, NCSE) B.1 NCSE with coma (including so-called “subtle” SE) B.2 NCSE without coma B.2.a. Generalized B.2.a.a Typical absence status B.2.a.b Atypical absence status B.2.a.c Myoclonic absence status B.2.b. Focal B.2.b.a Without impairment of consciousness (aura continua, with autonomic, sensory, visual, olfactory, gustatory, emotional/ psychic/experiential, or auditory symptoms) B.2.b.b Aphasic status B.2.b.c With impaired consciousness B.2.c Unknown whether focal or generalized B.2.c.a Autonomic SE Epilepsia, 56(10):1515–1523, 2015 Axis 2: Etiology • Known (i.e., symptomatic) - Acute (e.g., stroke, intoxication, malaria, encephalitis, etc.) - Remote (e.g., posttraumatic, postencephalitic, poststroke, etc.) - Progressive (e.g., brain tumor, Lafora’s disease and other PMEs, dementias) - SE in defined electroclinical syndromes • Unknown (i.e., cryptogenic) Epilepsia, 56(10):1515–1523, 2015 Axis 3: Electroencephalographic correlates • Currently there are no evidence-based EEG criteria for SE. Epilepsia, 56(10):1515–1523, 2015 EEG patterns in SE 1. Location: generalized (including bilateral synchronous patterns), lateralized, bilateral independent, multifocal. 2. Name of the pattern: Periodic discharges, rhythmic delta activity or spike-and-wave/sharp- and-wave plus subtypes. 3. Morphology: sharpness, number of phases (e.g., triphasic morphology), absolute and relative amplitude, polarity. 4. Time-related features: prevalence, frequency, duration, daily pattern duration and index, onset (sudden vs. gradual), and dynamics (evolving, fluctuating, or static). 5. Modulation: stimulus-induced vs. spontaneous. 6 Effect of intervention (medication) on EEG. Epilepsia, 56(10):1515–1523, 2015 Axis 4: Age 1. Neonatal (0 to 30 days) 2. Infancy (1 month to 2 years) 3. Childhood (> 2 to 12 years) 4. Adolescence and adulthood (> 12 to 59 years) 5. Elderly (≥ 60 years) Epilepsia, 56(10):1515–1523, 2015 American Clinical Neurophysiology Society’s Standardized Critical Care EEG Terminology: 2012 version J Clin Neurophysiol 2013;30: 1–27) Generalized convulsive status epilepticus (GCSE) Definition of CSE • CSE is a convulsive seizure lasting more than 5 min or consecutive seizures without recovery of consciousness. • In the case of convulsive SE, both time points (t1 at 5 min and t2 at 30 min) are based on animal experiments and clinical research. Epilepsia, 56(10):1515–1523, 2015 Key points • Principle of treatment 1. Stop both ongoing clinical and electrographic seizures 2. Identify and treat the etiology of CSE 3. diagnosis and treatment of complications of CSE Time is the brain • The response to treatment with anti-seizure medications is decreasing with time and ongoing seizures probably due to the following reasons; - Functional GABA receptors are decreased due to internalization of GABA receptors. - NMDA receptors are up-regulated. This can resulted in calcium influx intracellularly which makes seizure control more difficult and may causes cellular damage and secondary brain injury. - There is the upregulation of drug-efflux transporters such